Retinal pigment epithelial (RPE) cell death is thought to be the primary mechanism for the development of geographic atrophy (GA) in age-related macular degeneration (AMD). Along with choroidal neovascularization, GA is responsbile for most of the vision loss in AMD. Therefore the study of the exact mechanisms of RPE cell death are important to generate novel therapies for this condition. At present, no known treatments are available for GA. Evidence has been collected and now published on the programmed cell death pathway in RPE cells. We have been able to demonstrate that unlike the conventional programmed cell death pathways which utilize cytochrome c, caspase 3, 9 and PARP to initiate cell death, RPE cells have protective mechanisms which do not allow this pathway to become activated. Instead, the novel programmed cell death molecule, apoptosis induced factor (AIF) appears to be involved in RPE cell death. Additionally, growth factors which might be found in the retina, such as hepatocyte growth factor (HGF), appear to also protect the RPE cells from oxidative cell death. These findings are important since the use of exogenous HGF might become an important therapy for the prevention and treatment of GA associated with AMD.